Heat shock protein 90 beta (HSP90B) (HSP90B)

Heat shock protein 90 beta (HSP90B) is the constitutively expressed cytosolic isoform of the HSP90 molecular chaperone family, distinguished from the stress-inducible alpha isoform (UniProt P08238). It plays a fundamental role in the cellular proteostasis network by assisting in the folding, maturation, and stabilization of a diverse array of client proteins, including various kinases, transcription factors, and steroid receptors (Taipale et al., 2010, Nature Reviews Molecular Cell Biology). In many cancers, HSP90 beta is overexpressed or maintained in a high-activity state to stabilize oncogenic clients such as HER2, BCR-ABL, and mutated p53, thereby facilitating tumor growth and survival (Whitesell & Lindquist, 2005, Nature Reviews Cancer). Pharmacological targeting typically involves small-molecule inhibitors that bind to the N-terminal ATP-binding chaperone domain, which halts the chaperone cycle and leads to the degradation of client proteins via the ubiquitin-proteasome pathway (Neckers & Workman, 2012, Clinical Cancer Research). Despite the development of numerous inhibitors like ganetespib and pimitespib, clinical application has been hindered by challenges such as ocular and hepatic toxicities and the induction of the pro-survival heat shock response (Schopf et al., 2017, Nature Reviews Molecular Cell Biology).

Other names

HSP90AB1HSPCBHSP90-betaHeat shock 90kDa protein 1 betaCytosolic constitutively active Hsp90

Inhibition of the N-terminal ATP-binding domain, preventing the chaperone cycle and inducing the proteasomal degradation of oncogenic client proteins.